HM1.24 antigen was discovered as a membrane protein that is highly expressed in human myeloma cells. Then, it was demonstrated that a monoclonal antibody (anti-HM1.24 antibody) that was obtained from a mouse immunized with a human myeloma cell KPC-32 binds to human myeloma cells and plasma cells, and an antigen (HM1.24 antigen) that is recognized by the antibody is highly expressed in human myeloma cell lines such as RPMI8226 (Goto T. et al., Blood (1994), 84, 1922). It has also been reported that an anti-tumor effect can be obtained by the simultaneous administration of anti-HM1.24 antibody to a mouse that underwent the grafting of the human myeloma cell RPMI8226. Thereafter, the cDNA of HM1.24 antigen was obtained and the nucleotide sequence was determined, which revealed that the molecule was identical with Bst2 that had been reported to be a protein expressed in medullary stromal cells (Ishikawa, J. et al., Genomics (1995) 26, 527; International Patent Publication WO 95/10536).
On the other hand, in lymphatic tumors other than myeloma, it was found that HM1.24 antigen was expressed and that anti-HM1.24 antibody exhibits a cytotoxic activity based on antibody-dependent cell-mediated cytotoxicity (ADCC activity) and on complement-dependent cytotoxicity (CDC activity) and exhibits anti-tumor effect against lymphatic tumors (International Patent Publication WO 98/35698). It has also been demonstrated that the stimulation of hematopoietic tumors with interferon α or γ leads to an increase in the amount of HM1.24 antigen expressed, thereby enhancing the anti-tumor effect of anti-HM1.24 antibody (International Patent Publication WO 02/64159).
However, though the expression of HM1.24 antigen in hematopoietic tumors had been noted, its expression in solid tumors such as lung cancer, breast cancer and colon cancer was not known, nor was it known that it can damage solid tumor cells by ADCC.
As solid tumors except for hematopoietic tumors, there can be mentioned head and neck cancer, small cell lung cancer, non-small cell lung cancer (including squamous-cell carcinoma, adenocarcinoma, large cell carcinoma, adenosquamous carcinoma, and polymorphic sarcomatoid cancer, or cancer containing sarcoma components etc.), esophageal cancer, breast cancer, gastric cancer, colon cancer, rectal cancer, hepatic cancer, biliary tract cancer, pancreatic cancer, ovarian cancer, cervical cancer, endometrial cancer, prostate cancer, kidney cancer, bladder cancer, skin cancer, brain tumor, pediatric solid tumor, malignant bone tumor and the like.
Due to recent advances in medical technology, new therapeutic regimens have been proposed and attempted for these solid tumors, but they provide little therapeutic effect on solid tumor in the progressive stage and are still inadequate.